@article {349,
	title = {A postnatal role for embryonic myosin revealed by MYH3 mutations that alter TGFβ signaling and cause autosomal dominant spondylocarpotarsal synostosis.},
	journal = {Sci Rep},
	volume = {7},
	year = {2017},
	month = {2017 02 16},
	pages = {41803},
	abstract = {<p>Spondylocarpotarsal synostosis (SCT) is a skeletal disorder characterized by progressive vertebral, carpal and tarsal fusions, and mild short stature. The majority of affected individuals have an autosomal recessive form of SCT and are homozygous or compound heterozygous for nonsense mutations in the gene that encodes the cytoskeletal protein filamin B (FLNB), but a subset do not have FLNB mutations. Exome sequence analysis of three SCT patients negative for FLNB mutations identified an autosomal dominant form of the disease due to heterozygosity for missense or nonsense mutations in MYH3, which encodes embryonic myosin. Cells transfected with the MYH3 missense mutations had reduced TGFβ signaling, revealing a regulatory role for embryonic myosin in the TGFβ signaling pathway. In wild-type mice, there was persistent postnatal expression of embryonic myosin in the small muscles joining the neural arches of the spine suggesting that loss of myosin function in these muscles contribute to the disease. Our findings demonstrate that dominant mutations in MYH3 underlie autosomal dominant SCT, identify a postnatal role for embryonic myosin and suggest that altered regulation of signal transduction in the muscles within the spine may lead to the development of vertebral fusions.</p>},
	keywords = {Abnormalities, Multiple, Alleles, Bone Morphogenetic Proteins, Cytoskeletal Proteins, Female, Genes, Dominant, Genotype, Humans, Lumbar Vertebrae, Male, Musculoskeletal Diseases, Mutation, Myosins, Phenotype, Radiography, Scoliosis, Signal Transduction, Synostosis, Thoracic Vertebrae, Transforming Growth Factor beta, Whole Exome Sequencing},
	issn = {2045-2322},
	doi = {10.1038/srep41803},
	author = {Zieba, Jennifer and Zhang, Wenjuan and Chong, Jessica X and Forlenza, Kimberly N and Martin, Jorge H and Heard, Kelly and Grange, Dorothy K and Butler, Merlin G and Kleefstra, Tjitske and Lachman, Ralph S and Nickerson, Deborah and Regnier, Michael and Cohn, Daniel H and Bamshad, Michael and Krakow, Deborah}
}
@article {319,
	title = {Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm.},
	journal = {Nat Genet},
	volume = {44},
	year = {2012},
	month = {2012 Nov},
	pages = {1249-54},
	abstract = {<p>Elevated transforming growth factor (TGF)-β signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). However, the location and character of many of the causal mutations in LDS intuitively imply diminished TGF-β signaling. Taken together, these data have engendered controversy regarding the specific role of TGF-β in disease pathogenesis. Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm. We identified causative variation in ten individuals with SGS in the proto-oncogene SKI, a known repressor of TGF-β activity. Cultured dermal fibroblasts from affected individuals showed enhanced activation of TGF-β signaling cascades and higher expression of TGF-β-responsive genes relative to control cells. Morpholino-induced silencing of SKI paralogs in zebrafish recapitulated abnormalities seen in humans with SGS. These data support the conclusions that increased TGF-β signaling is the mechanism underlying SGS and that high signaling contributes to multiple syndromic presentations of aortic aneurysm.</p>},
	keywords = {Animals, Aortic Aneurysm, Arachnodactyly, Cells, Cultured, Craniosynostoses, DNA-Binding Proteins, Fibroblasts, Humans, Loeys-Dietz Syndrome, Marfan Syndrome, Mice, Mutation, Phenotype, Phosphorylation, Proto-Oncogene Proteins, Signal Transduction, Transforming Growth Factor beta, Zebrafish},
	issn = {1546-1718},
	doi = {10.1038/ng.2421},
	author = {Doyle, Alexander J and Doyle, Jefferson J and Bessling, Seneca L and Maragh, Samantha and Lindsay, Mark E and Schepers, Dorien and Gillis, Elisabeth and Mortier, Geert and Homfray, Tessa and Sauls, Kimberly and Norris, Russell A and Huso, Nicholas D and Leahy, Dan and Mohr, David W and Caulfield, Mark J and Scott, Alan F and Destr{\'e}e, Anne and Hennekam, Raoul C and Arn, Pamela H and Curry, Cynthia J and Van Laer, Lut and McCallion, Andrew S and Loeys, Bart L and Dietz, Harry C}
}
